Adherence, Persistence, and Switching Patterns of Dabigatran Etexilate | Page 3
Published Online: September 16, 2013
Kimberly Tsai, PharmD; Sara C. Erickson, PharmD; Jianing Yang, MS; Ann S. M. Harada, PhD, MPH; Brian K. Solow, MD; and Heidi C. Lew, PharmD
The results of this study should be interpreted with caution, as it was not possible to verify reasons for dabigatran discontinuation. Potential reasons may include adverse event occurrence (eg, a bleeding episode or dyspepsia as was observed in the RE-LY trial8), a switch to aspirin or rivaroxaban, or use of dabigatran for an off-label indication with a shorter duration of treatment. In terms of adverse events, in the RE-LY trial,8 reasons for discontinuation that were reported included gastrointestinal bleeding, gastrointestinal symptoms, a serious adverse event, an outcome event, and patient’s decision. (For reference, in the RE-LY trial,8 gastrointestinal bleeding was cited as the reason for discontinuation in 1.3% of patients taking dabigatran 150 mg vs 0.9% of patients who were taking warfarin [P value not reported]. Gastrointestinal side effects led to discontinuation in 2.1% of patients taking 150 mg dabigatran vs 0.6% of patients who were taking warfarin [P value not reported].) Rivaroxaban was initially approved in the United States on July 1, 2011, for the prevention of deep vein thrombosis (DVT) in patients undergoing knee or hip replacement surgery. According to the time frame of this study (with the latest possible day of the post-index period as December 31, 2011), some patients could have switched from dabigatran to rivaroxaban, accounting for some of the nonpersistence. However, this is less likely, as a very low incidence of switching from dabigatran to rivaroxaban was observed in a prescription claims study examining switch rates among oral anticoagulants (warfarin, dabigatran, and rivaroxaban).9 The study found that only 0.02% of switchers changed from dabigatran to rivaroxaban, while 87.3% of switchers changed from warfarin to dabigatran. Lastly, it is possible that some discontinuation occurred appropriately and may be accounted for by patients who were treated with dabigatran, off label, for a fi nite duration (eg, DVT prophylaxis in patient undergoing knee or hip replacement surgery). However, it is less likely that this accounts for the majority of discontinuations observed in this study, for several reasons. First, dabigatran required Prior Authorization (PA) approval for benefit coverage in this population. A review of PA cases among Part D patients during a 4-month period found that less than 1% had off-label indications for finite duration of dabigatran therapy, and the majority of indications were for atrial fi brillation,requiring chronic dabigatran therapy. Secondly, the findings of an observational study reported that during the identification period of our study (October 29, 2010, through June 30, 2011), the majority of patients in the United States were using dabigatran for the atrial fi brillation indication.10 The research utilized the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to quantify patterns of oral anticoagulant use for the prevention of thromboembolism. The authors found that dabigatran has been rapidly adopted into ambulatory practice in the United States, primarily for the treatment of atrial fi brillation, but increasingly is being used for off-label indications. They found that the proportion of US patients who used dabigatran for the indication of atrial fi brillation was 92% in the last quarter of 2010 and 63% in the last quarter of 2011. Thus, we believe that the majority of discontinuations observed in our study are due to true nonpersistence, rather than appropriate discontinuations for off-label indications. A follow-up study, with pharmacy and medical claims, could offer explanations for nonpersistence (eg, capturing a medical claim with the ICD-9-CM diagnosis code for hemorrhage of gastrointestinal tract may indicate that a patient discontinued because of a gastrointestinal bleed).
Limitations of this prescription claims database study include lack of information regarding diagnoses and medical claims. Comorbidities were inferred from pharmacy claims, by assuming that taking certain medications indicates the presence of a particular disease state. (Validation of the proxy measures was done by reviewing published studies and referencing an internal process performing similar identifications of disease states through pharmacy claims.) Secondly, measures of adherence and persistence were based on claims data, which assumes that the patient is taking the medication rather than stockpiling it. It is not possible in a claims analysis to determine whether patients discontinued at their own discretion or upon the direction of their healthcare provider, nor is it possible to determine reasons behind discontinuations of therapy. Having this information could aid in the design of potential specific interventions to increase adherence and persistence to therapy. Lastly, claims data do not capture plan exclusion OTC utilization or other patient out-of-pocket purchases, which could contribute to a more comprehensive understanding of patient practices.
Two in 5 patients discontinued dabigatran therapy within 6 months in this observational, retrospective analysis using administrative pharmacy claims from a large PBM. The majority of patients discontinuing dabigatran therapy were not anticoagulated with warfarin during the post-index period. These findings highlight potential gaps in the care of patients treated with dabigatran therapy in routine practice. Patients should be educated to report intolerance, adverse events, or cost burden to their healthcare provider, instead of discontinuing therapy on their own. Due to the dependence on good adherence and persistence to dabigatran therapy for prevention of stroke and thromboembolic events, there may be a need for healthcare professionals and managed care organizations to provide additional patient support and counseling on this medication. Further research is needed to explain the reasons for nonpersistence to dabigatran therapy.
Author Affiliations: From OptumRx (KT, SCE, JY, ASMH, BKS, HCL), Irvine, CA.
Funding Source: None.
Author Disclosures: The authors (KT, SCE, JY, ASMH, BKS, HCL) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (KT, SCE, BKS, HCL); acquisition of data (KT, JY); analysis and interpretation of data (KT, SCE, JY, ASMH, BKS); drafting of the manuscript (KT, SCE, ASMH); critical revision of the manuscript for important intellectual content (KT, SCE, ASMH); statistical analysis (KT, JY); provision of study materials or patients (KT); administrative, technical, or logistic support (ASMH, BKS, HCL); and supervision (SCE, BKS, HCL).
Address correspondence to: Kimberly Tsai, PharmD, 2300 Main St, CA 134-0404, Irvine, CA 92614. E-mail: email@example.com.
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